VAS2870 抑制人脐静脉内皮细胞中组胺诱导的钙信号和 vWF 分泌。
VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells.
机构信息
Koltsov Institute of Developmental Biology, Moscow 119334, Russia.
Sechenov Institute of Evolutional Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg 194223, Russia.
出版信息
Cells. 2019 Feb 23;8(2):196. doi: 10.3390/cells8020196.
In this study, we investigated the effects of NAD(P)H oxidase (NOX) inhibitor VAS2870 (3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine) on the histamine-induced elevation of free cytoplasmic calcium concentration ([Ca]) and the secretion of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVECs) and on relaxation of rat aorta in response to histamine. At 10 μM concentration, VAS2870 suppressed the [Ca] rise induced by histamine. Inhibition was not competitive, with IC50 3.64 and 3.22 μM at 1 and 100 μM concentrations of histamine, respectively. There was no inhibition of [Ca] elevation by VAS2870 in HUVECs in response to the agonist of type 1 protease-activated receptor SFLLRN. VAS2870 attenuated histamine-induced secretion of vWF and did not inhibit basal secretion. VAS2870 did not change the degree of histamine-induced relaxation of rat aortic rings constricted by norepinephrine. We suggest that NOX inhibitors might be used as a tool for preventing thrombosis induced by histamine release from mast cells without affecting vasorelaxation.
在这项研究中，我们研究了 NAD(P)H 氧化酶 (NOX) 抑制剂 VAS2870（3-苄基-7-(2-苯并恶唑基)硫代-1,2,3-三唑并[4,5-d]嘧啶）对人脐静脉内皮细胞 (HUVEC) 中组胺诱导的游离细胞质钙离子浓度 ([Ca]) 升高和血管性血友病因子 (vWF) 分泌的影响，以及对组胺引起的大鼠主动脉松弛的影响。在 10 μM 浓度下，VAS2870 抑制了组胺诱导的 [Ca] 升高。抑制不是竞争性的，IC50 在 1 和 100 μM 浓度的组胺下分别为 3.64 和 3.22 μM。VAS2870 对 HUVEC 中 1 型蛋白酶激活受体 SFLLRN 激动剂引起的 [Ca] 升高没有抑制作用。VAS2870 减弱了组胺诱导的 vWF 分泌，而不抑制基础分泌。VAS2870 并未改变由去甲肾上腺素收缩的大鼠主动脉环中组胺诱导的松弛程度。我们认为，NOX 抑制剂可作为预防组胺从肥大细胞释放引起的血栓形成的工具，而不影响血管舒张。
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